Since 2000, Fox Chase Cancer Center has partnered with the Blokhin Cancer Center in Russia to foster the training of Russian oncologists and to facilitate international research to reduce cancer morbidity and mortality. To this end, the centers have been studying issues related to treating nicotine addiction among cancer patients. This proposal will extend this research by focusing on the biobehavioral aspects of nicotine addiction. Genetic polymorphisms that affect the release and availability of dopamine may account for the extreme variability in the ability to quit smoking. Most research in this area has assessed polymorphisms on dopamine receptor genes DRD2 and DRD4 and polymorphisms in the dopamine transporter gene SLC6A3. New genes have also been recently examined such as the cannabinoid CB1 receptor. Replication in this area has been hampered by: 1) ethnic admixture, which can cause population stratification bias; 2) use of crude and varying assessments of smoking phenotypes; 3) a reliance on cross-sectional data; and 4) use of small samples, which prevent the assessment of gene-environment and gene-gene interactions. In this study, we will consider these methodological issues and: 1) Assess the prevalence of DRD2, DRD4, SLC6A3 genotypes, and the CB1 receptor in a sample of newly diagnosed cancer patients and correlate these genes with smoking status; 2) Examine whether or not and to what degree these genes predict cessation longitudinally; 3) Evaluate the interaction among these genes in terms of predicting smoking status; and 4) Explore the interaction between depressive symptoms and these genes in terms of predicting smoking status. If genetic studies of nicotine addiction are to lead to personalized treatments for smoking and novel methods for prevention, studies that consider these methodological issues are needed. Such research also addresses a major public health problem in Russia, facilitates the development of expertise at the Blokhin Cancer Center, and advances the field of nicotine addiction treatment more broadly.